Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.290887
Title: Studies on the phosphonic acid analogues of gamma-aminobutyric acid and L-glutamic acid
Author: Turner, P. D.
ISNI:       0000 0001 3539 4490
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 1980
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Abstract:
The phosphonate compounds 3-aminopropylphosphonate (APP) and 2-amino-4-phosphonobutyrate were assessed as analogues of gamma-aminobutyrate (GABA) and L-glutamate, respectively, in a range of systems involved in the neurotransmitter roles of GABA and L-glutamate in mammalian brain. These systems included sites for post-synaptic binding and high-affinity uptake and a number of enzymes. APP was shown to inhibit the binding of GABA to its post-synaptic receptor, having an IC50 value of 7.08 mM and, at 2.0 mM, to have no effect on the high-affinity uptake of GABA. APP inhibited GABA:2-oxoglutarate aminotransferase (E.C.2.6.1.19) by 58% at 25 mM and was a substrate for this enzyme (17% of the rate obtained with 25 mM-GABA). APB (at 1.0 mM) was shown not to interact with the high affinity uptake system for L-glutamate and had no effect on L-glutamate:oxaloacetate aminotransferase (E.C.2.6.1.1) at 25.0 mM. At 10.0 mM APB inhibited L-alanine:2-oxoglutarate aminotransferase (E.C.2.6.1.2) by 11% and L-glutamate decarboxylase (E.C.4.1.1.15) by 29% but had no effect on L-glutamine synthetase (E.C.6.3.1.2). APB inhibited L-glutamate dehydrogenase (E.C.1.4.1.2) and kinetic analysis showed that three inhibition mechanisms were possible all of which involved binding by APB to both the L-glutamate and NAD+ binding sites. True Ki values were determined and were between 0.1 and 4.0 mM.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.290887  DOI: Not available
Keywords: Chemistry, general
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